Peptides derived from each of the endogenous opioid precursors were measured in gerbil brain regions after transient ischemia. Lasting depletion of dynorphin A immunoreactivity were observed only in hippocampus. Levels of hippocampal dynorphin fell by 30- 40% as early as 1 hr after recirculation and remained at 50% of control for at least one week. In some experiments peptide levels showed a transient recovery at 24 hr. Preliminary results suggest a similar reduction in hippocampal pro-dynorphin mRNA levels with a similar time course. These results demonstrate at the neurochemical level a unique sensititivity of the dynorphin-containing dentate granule cell/mossy fiber pathway to transient ischemia. Although these cells remain histologically intact, the decrease in dynorphin precedes and continues during the delayed loss of hippocampal CA1 neurons characteristic of this model and further defines the selective vulnerability of hippocampal circuitry following ischemia. The mechanisms responsible for peptide depletion, and the functional roles of dynorphin peptides in the physiology and pathology of the hippocampus, remain to be elucidated.